Metabolism of prostaglandin E2 in the isolated perfused kidney of the rabbit

In the Krebs-perfused rabbit isolated kidney, [³H]PGE₂ (5 μCi, 165 Ci/mmole) was infused intra-arterially for 5 min; venous and urinary effluents were collected every 2 min for 20 min. Efflux of radioactive material peaked at 8 min and declined thereafter. The kidney retained 35% of the infused ³H. Samples were extracted for acidic lipids; PGE₂, PGF_2α and metabolites were separated by TLC and quantified by a radiometric method. Efflux of [³H]PGF_2α into urinary and venous outflows increased progressively over the first 12 min and then plateaued for the remaining 4 min. By 12 min, conversion of [³H]PGE₂ to [³H]PGF_2α was 70 and 80% as determined by radiolabeled products recovered in the urinary and venous effluents respectively. Estimates of total conversion of [³H]PGE₂ to [³H]PGF_2α were 62 and 52% of the radiolabeled material exiting in the urinary and venous effluents respectively. The 15-keto and 13,14-dihydro-15-keto metabolites of [³H]PGF_2α appeared in the urine but were not found in the venous outflow. We conclude that PGE-9-ketoreductase (PGE-9KRD) activity is high in the rabbit isolated perfused kidney. Further, the extent of conversion of PGE₂ to PGF_2α and metabolism of newly formed PGF_2α may differ within the vascular and tubular compartments of the kidney. PGE-9KRD activity may be important in the regulation of renal vascular tone, compliance of veins, and salt and water balance.